TY - JOUR
T1 - Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.
AU - Wataya, Yusuke
AU - Naito, Tomoharu
AU - Sato, Akira
AU - Hiramoto, Akiko
AU - Kitade, Yukio
AU - Sasaki, Takuma
AU - Matsuda, Akira
AU - Fukushima, Masakazu
AU - Kim, Hye Sook
PY - 2009
Y1 - 2009
N2 - 1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We have investigated the cancer-cell death induced by ECyd, focusing on its molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L was unknown. To investigate the mechanism, we performed the identification of RNase L-binding partners by proteomic approach using co-immunoprecipitation and mass spectrometry. We found that RNase L was associated with a protein (we named it Protein-190). At the same time, we observed that Protein-190 was amply phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced apoptosis was supported by a knockdown experiment using small interfering RNA (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically decreased when Protein-190 was knocked-down. These results indicated Protein-190 as a regulator in apoptosis, and provide the possibility for a new clinical target in cancer chemotherapy.
AB - 1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We have investigated the cancer-cell death induced by ECyd, focusing on its molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L was unknown. To investigate the mechanism, we performed the identification of RNase L-binding partners by proteomic approach using co-immunoprecipitation and mass spectrometry. We found that RNase L was associated with a protein (we named it Protein-190). At the same time, we observed that Protein-190 was amply phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced apoptosis was supported by a knockdown experiment using small interfering RNA (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically decreased when Protein-190 was knocked-down. These results indicated Protein-190 as a regulator in apoptosis, and provide the possibility for a new clinical target in cancer chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=77952540498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952540498&partnerID=8YFLogxK
U2 - 10.1093/nass/nrp146
DO - 10.1093/nass/nrp146
M3 - Article
C2 - 19749375
AN - SCOPUS:77952540498
SP - 291
EP - 292
JO - Nucleic acids symposium series (2004)
JF - Nucleic acids symposium series (2004)
SN - 1746-8272
IS - 53
ER -